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Although inhibition of T cell coinhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. In the present study, we show that type 1 interferon (IFN-I) regulates coinhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses established the dynamic regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors (TFs) and TF footprint analysis revealed two regulator modules with different temporal kinetics that control expression of coinhibitory receptors and IFN-I response genes, with SP140 highlighted as one of the key regulators that differentiates LAG-3 and TIGIT expression. Finally, we found that the dynamic IFN-I response in vitro closely mirrored T cell features in acute SARS-CoV-2 infection. The identification of unique TFs controlling coinhibitory receptor expression under IFN-I response may provide targets for enhancement of immunotherapy in cancer, infectious diseases and autoimmunity.
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COVID-19 , Interferón Tipo I , Redes Reguladoras de Genes , Humanos , Interferón Tipo I/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Inmunológicos/genética , SARS-CoV-2 , Linfocitos TRESUMEN
CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8+-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors. T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137 agonists favored tumor growth, anti-PD1 efficacy was improved with subsequent CD137 stimulation in pre-clinical mouse models. Better understanding of T cell exhaustion has crucial implications for the treatment of cancer and infectious diseases. Our results identify CD137 as a critical regulator of Tex cell expansion and differentiation that holds potential for broad therapeutic applications.
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Linfocitos T CD8-positivos , Neoplasias , Ratones , Animales , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral , Diferenciación Celular , Proliferación Celular , Receptores de Antígenos de Linfocitos TRESUMEN
KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).
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Malformaciones Arteriovenosas , Proteínas Proto-Oncogénicas p21(ras) , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/tratamiento farmacológico , Malformaciones Arteriovenosas/genética , Modelos Animales de Enfermedad , Mutación con Ganancia de Función , Mutación , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Piridinas/uso terapéutico , Pirimidinas , Fármacos Cardiovasculares/uso terapéutico , Adulto JovenRESUMEN
The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.
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Programas Informáticos , Humanos , Biología Computacional/métodos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/citología , Genómica/métodos , Análisis de DatosRESUMEN
The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call for a better stratification of patients based on immune components. The most pressing being cytotoxic lymphocytes such as Natural Killer (NK) cells that are mandatory for MM surveillance and therapy. In this study, we performed a single cell RNA sequencing analysis of NK cells from 10 MM patients and 10 age/sex matched healthy donors (HD) that revealed important transcriptomic changes in NK cell landscape affecting both the bone marrow and peripheral blood compartment. The frequency of mature cytotoxic "CD56dim" NK cell subsets was reduced in MM patients at the advantage of late-stage NK cell subsets expressing NFï«B and IFN-I inflammatory signatures. These NK cell subsets accumulating in MM patients were characterized by a low CD16 and CD226 expression and poor cytotoxic functions. MM CD16/CD226Lo NK cells also had adhesion defects with reduced LFA-1 integrin activation and actin polymerization that may account for their limited effector functions in vitro. Finally, analysis of BM infiltrating NK cells in a retrospective cohort of 177 MM patients from the IFM 2009 trial demonstrated that a high frequency of NK cells and their low CD16 and CD226 expression were associated with a shorter overall survival. Thus, CD16/CD226Lo NK cells with reduced effector functions accumulate along MM development and negatively impact patients' clinical outcome. Given the growing interest in harnessing NK cells to treat myeloma, this improved knowledge around MM-associated NK cell dysfunction will stimulate the development of more efficient immunotherapeutic drugs against MM.
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BACKGROUND: Understanding the natural history of human papillomavirus (HPV) infections is essential to cervical cancer prevention planning. We estimated HPV type-specific infection detection and clearance in young women. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) study is a prospective cohort of 502 college-age women who recently initiated a heterosexual relationship. We tested vaginal samples collected at 6 clinical visits over 24 months for 36 HPV types. Using rates and Kaplan-Meier analysis, we estimated time-to-event statistics with 95% confidence intervals (CIs) for detection of incident infections and clearance of incident and present-at-baseline infections (separately). We conducted analyses at the woman- and HPV-levels, with HPV types grouped by phylogenetic relatedness. RESULTS: By 24 months, we detected incident infections in 40.4% (CI, 33.4%-48.4%) of women. Incident subgenus 1 (43.4; CI, 33.6-56.4), 2 (47.1; CI, 39.9-55.5), and 3 (46.6; CI, 37.7-57.7) infections cleared at similar rates per 1000 infection-months. We observed similar homogeny in HPV-level clearance rates among present-at-baseline infections. CONCLUSIONS: Our analyses provide type-specific infection natural history estimates for cervical cancer prevention planning. HPV-level analyses did not clearly indicate that high oncogenic risk subgenus 2 infections persist longer than their low oncogenic risk subgenera 1 and 3 counterparts.
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Infecciones por Papillomavirus , Enfermedades de Transmisión Sexual , Neoplasias del Cuello Uterino , Humanos , Femenino , Heterosexualidad , Neoplasias del Cuello Uterino/epidemiología , Estudios Prospectivos , Filogenia , Papillomaviridae/genética , Genitales , Factores de Riesgo , IncidenciaRESUMEN
Underprioritization of mental health is a global problem and threatens the decades-long progress of the US President's Emergency Plan for AIDS Relief (PEPFAR) program. In recent years, mental health has become globally recognized as a part of universal healthcare, making this an opportune moment for the global community to integrate mental health services into routine programming. PEPFAR is well positioned to lead by example. We conceptualized 5 key strategies that might help serve as a framework to support mental health programming as part of PEPFAR's current 5-year strategic plan. PEPFAR and the global community have an opportunity to identify mental health service gaps and interweave global mental health priorities with actions to end the HIV and TB epidemics by 2030.
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Epidemias , Infecciones por VIH , Servicios de Salud Mental , Tuberculosis , Humanos , Salud Mental , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Infecciones por VIH/epidemiologíaRESUMEN
The Lubricant Investigation in Men to Inhibit Transmission of human papillomavirus (HPV) Infection randomized control trial in gay, bisexual, and other men who have sex with men (gbMSM) found that carrageenan use neither reduced acquisition of anal HPV infections nor influenced infection clearance. To investigate carrageenan's lack of protective effect, we compared the change in anal HPV16 and HPV18 viral loads following carrageenan use against placebo. We restricted our analysis to participants who completed the first four study visits and had a valid baseline sample (n = 161, 54 HIV-positive). Samples were tested for HPV detection using the linear array PCR assay. HPV16- and/or HPV18-positive samples were tested for viral load using real-time PCR. For participants who tested HPV16- (n = 29) or HPV18-positive (n = 10) at least once across visits 1-4, we compared the change in type-specific viral load between study arms using the Mann-Whitney U test. Although the median net change in HPV16 and HPV18 viral loads across visits 1-4 was higher in the treatment than placebo arm (HPV16: 0.68 vs. 0.18 copies/cell, p = 0.60; HPV18: 18.32 vs. 10.12 copies/cell, p = 0.52), these differences were not statistically significant. Results were similar by HIV status. Carrageenan use did not impact anal HPV16 or HPV18 viral loads, which may further explain its lack of protective effect in gbMSM.
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Infecciones por Papillomavirus , Minorías Sexuales y de Género , Humanos , Masculino , Carragenina , Homosexualidad Masculina , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/prevención & control , Carga ViralRESUMEN
Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51.
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Alphapapillomavirus , Infecciones por Papillomavirus , Enfermedades de Transmisión Sexual , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/prevención & control , Carragenina , Carga Viral , Virus del Papiloma Humano , Cuello del Útero , Papillomaviridae/genética , ADN Viral/análisisRESUMEN
Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Tuberculosis , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Cooperación Internacional , Tuberculosis/epidemiología , Tuberculosis/prevención & control , África , Antirretrovirales/uso terapéuticoRESUMEN
PURPOSE: Diffuse midline gliomas (DMG) with H3K27 alterations (H3K27M-DMG) are a highly aggressive form of brain cancer. In rare cases, H3K27 mutations have been observed in diffuse non-midline gliomas (DNMG). It is currently unclear how these tumors should be classified. Herein, we analyze the characteristics of DNMG with H3K27M mutations. METHODS: We reviewed the clinical, radiological and histological characteristics of all patients with an H3K27M mutated diffuse glioma diagnosed in our institution, between 2016 and 2023, to identify cases with a non-midline location. We then performed a molecular characterization (DNA methylation profiling, whole genome and transcriptome sequencing or targeted sequencing) of patients with an H3K27M-mutant DNMG and reviewed previously reported cases. RESULTS: Among 51 patients (18 children and 33 adults) diagnosed with an H3K27M diffuse glioma, we identified two patients (4%) who had a non-midline location. Including our two patients, 39 patients were reported in the literature with an H3K27M-mutant DNMG. Tumors were most frequently located in the temporal lobe (48%), affected adolescents and adults, and were associated with a poor outcome (median overall survival was 10.3 months (0.1-84)). Median age at diagnosis was 19.1 years. Tumors frequently harbored TP53 mutations (74%), ATRX mutations (71%) and PDGFRA mutations or amplifications (44%). In DNA methylation analysis, H3K27M-mutant DNMG clustered within or close to the reference group of H3K27M-mutant DMG. Compared to their midline counterpart, non-midline gliomas with H3K27M mutations seemed more frequently associated with PDGFRA alterations. CONCLUSION: DNMG with H3K27M mutations share many similarities with their midline counterpart, suggesting that they correspond to a rare anatomical presentation of these tumors. This is of paramount importance, as they may benefit from new therapeutic approaches such as ONC201.
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We report a case of congenital multisystem Langerhans cell histiocytosis with cutaneous and hematopoietic involvement. After the failure of first-line (vinblastine and prednisolone) and second-line (vincristine and cytarabine) therapies, treatment with cobimetinib, a mitogen-activated protein kinase (MEK) inhibitor, led to the remission of disease and a sustained response after 11 months of ongoing treatment. Protein kinase inhibitors targeting BRAF or MEK could represent a promising future therapeutic option, also in children with LCH.
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Azetidinas , Histiocitosis de Células de Langerhans , Piperidinas , Humanos , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/congénito , Azetidinas/uso terapéutico , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Masculino , Femenino , LactanteRESUMEN
BACKGROUND: Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. METHODS: We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. RESULTS: At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58-52 (r = 0.86), 58-33 (r = 0.75), 33-52 (r = 0.72), and between GST-E6: 52-11 (r = 0.84), 52-18 (r = 0.79), 58-33 (r = 0.78), 35-11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%-62.2%). CONCLUSIONS: Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.
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Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Femenino , Estudios de Cohortes , Virus del Papiloma Humano , Filogenia , Anticuerpos Antivirales , Papillomavirus Humano 16 , Proteínas de la Cápside/genética , Genotipo , Proteínas Oncogénicas Virales/genéticaRESUMEN
Preclinical studies have demonstrated carrageenan's anti-human papillomavirus (HPV) activity. We assessed efficacy of a carrageenan-based gel compared to a placebo gel in increasing the clearance of anal HPV infections among gay, bisexual, and other men who have sex with men (gbMSM). Of 255 enrolled gbMSM, 134 were HPV positive at baseline and had valid HPV results for ≥2 visits. Carrageenan did not differ from placebo in clearing all baseline infections (hazard ratio,â 0.84 [95% confidence interval, .31-2.27]), based on having 2 consecutive HPV-negative visits following at least 1 HPV-positive visit. There were no remarkable differences for analyses at the HPV type level or by human immunodeficiency virus status. CLINICAL TRIALS REGISTRATION: NCT02354144.
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Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Carragenina , Canal Anal , Virus del Papiloma Humano , PapillomaviridaeRESUMEN
The present study investigates the statistics and spectral content of natural vestibular stimuli experienced by healthy human subjects during three unconstrained activities. More specifically, we assessed how the characteristics of vestibular inputs are altered during the operation of a complex human-machine interface (a flight in a helicopter simulator) compared with more ecological tasks, namely a walk in an office space and a seated visual exploration task. As previously reported, we found that the power spectra of vestibular stimuli experienced during self-navigation could be modeled by two power laws but noted a potential effect of task intensity on the transition frequency between the two fits. In contrast, both tasks that required a seated position had power spectra that were better described by an inverted U shape in all planes of motion. Taken together, our results suggest that 1) walking elicits stereotyped vestibular inputs whose power spectra can be modeled by two power laws that intersect at a task intensity-dependent frequency; 2) body posture induces changes in the frequency content of vestibular information; 3) pilots tend to operate their aircraft in a way that does not generate highly nonecological vestibular stimuli; and 4) nevertheless, human-machine interfaces used as a means of manual navigation still impose some unnatural, contextual constraints on their operators.NEW & NOTEWORTHY Building upon previously published research, this study assesses and compares the vestibular stimuli experienced by healthy subjects in natural tasks and during the interaction with a complex machine: a helicopter simulator. Our results suggest the existence of an anatomical filter, meaning that body posture shapes vestibular spectral content. Our findings further indicate that operators control their machine within a constrained operating range such that they experience vestibular stimulations that are as ecological as possible.
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Vestíbulo del Laberinto , Humanos , Postura , Movimiento (Física) , Aeronaves , Orientación EspacialRESUMEN
Targeting EGFR alterations, particularly the L858R (Exon 21) mutation and Exon 19 deletion (del19), has significantly improved the survival of lung cancer patients. From now on, the issue is to shorten the time to treatment. Here, we challenge two well-known rapid strategies for EGFR testing: the cartridge-based platform Idylla™ (Biocartis) and a digital droplet PCR (ddPCR) approach (ID_Solution). To thoroughly investigate each testing performance, we selected a highly comprehensive cohort of 39 unique del19 (in comparison, the cbioportal contains 40 unique del19), and 9 samples bearing unique polymorphisms in exon 19. Additional L858R (N = 24), L861Q (N = 1), del19 (N = 63), and WT samples (N = 34) were used to determine clear technical and biological cutoffs. A total of 122 DNA samples extracted from formaldehyde-fixed samples was used as input. No false positive results were reported for either of the technologies, as long as careful droplet selection (ddPCR) was ensured for two polymorphisms. ddPCR demonstrated higher sensitivity in detecting unique del19 (92.3%, 36/39) compared to Idylla (67.7%, 21/31). However, considering the prevalence of del19 and L858R in the lung cancer population, the adjusted theranostic values were similar (96.51% and 95.26%, respectively). ddPCR performs better for small specimens and low tumoral content, but in other situations, Idylla is an alternative (especially if a molecular platform is absent).
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Técnicas de Diagnóstico Molecular , Mutación , Reacción en Cadena de la Polimerasa/métodos , Medicina de PrecisiónRESUMEN
Bone metastases of hepatocellular carcinoma (HCC) are rare and disease-revealing bone metastasis are exceptional. Here, we report the case of a 69-year-old man with a cervical vertebral metastasis of hepatocellular carcinoma. Morphological aspect of a metastatic tumor with eosinophilic and polygonal cells raises the question of the differential diagnosis between a localization of a hepatocellular carcinoma or an hepatoid carcinoma, notably when the metastasis is the first clinical manifestation. The morphological aspect by itself does not provide strong enough arguments for diagnosis. Well selected immunohistochemical markers can sometimes help to orientate towards one of the two hypotheses, in particular SALL4 and LIN28 which are in favour of hepatoid carcinoma when both are positive. Finally, as these two entities have different molecular profiles, molecular study can also be helpful to distinguish them. Indeed, HCCs often present TERT promoter, CTNNB1 mutations and IL-6/JAK/STAT pathway activation while hepatoid adenocarcinoma frequently presents chromosome 20 long arm gain. TP53 mutations are found in both entities and are therefore not discriminating. Differential diagnosis is important because the treatment will be that of the primary. Prognostic data for HCC revealed by bone metastasis are scarce, although they seem to be associated with a poor prognosis, with a 1 to 2 months overall survival. There is currently no data for hepatoid adenocarcinoma with bone metastasis.
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Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Gástricas , Masculino , Humanos , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/secundario , Quinasas Janus/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Gástricas/patología , Inmunohistoquímica , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Adenocarcinoma/patología , Diagnóstico DiferencialRESUMEN
BACKGROUND: Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners' infections with the same human papillomavirus (HPV) type. METHODS: We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive. RESULTS: We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3-5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio,â 1.1 [95% confidence interval, .5-2.1], for 3-5 vs none). CONCLUSIONS: We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.
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Infecciones por Papillomavirus , Alelos , Estudios de Cohortes , Antígenos HLA/genética , Heterosexualidad , Humanos , Papillomaviridae/genéticaRESUMEN
BACKGROUND: Previous studies examining the association between male circumcision (MC) and human papillomavirus (HPV) infections have reported inconsistent results. We used data from the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study to examine the association between MC and HPV infections in males and their female sexual partners. METHODS: We enrolled monogamous couples in a longitudinal study between 2005 and 2011 in Montreal, Canada. We used logistic and Poisson regression models with propensity score adjustment to estimate odds ratios (ORs) and rate ratios for the association between MC and the prevalence, transmission, and clearance of HPV infections. RESULTS: Four hundred thirteen couples were included in our study. The prevalence OR for the association between MC and baseline infections was 0.81 (95% confidence interval [CI], .56-1.16) in males and 1.05 (95% CI, .75-1.46) in females. The incidence rate ratio for infection transmission was 0.59 (95% CI, .16-2.20) for male-to-female transmission and 0.77 (95% CI, .37-1.60) for female-to-male transmission. The clearance rate ratio for clearance of infections was 0.81 (95% CI, .52-1.24). CONCLUSIONS: We found little evidence of an association between MC and HPV infection prevalence, transmission, or clearance in males and females. Further longitudinal couple-based studies are required to investigate this association.
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Alphapapillomavirus , Circuncisión Femenina , Circuncisión Masculina , Infecciones por Papillomavirus , Enfermedades de Transmisión Sexual , Estudios de Cohortes , Femenino , Genitales , Heterosexualidad , Humanos , Estudios Longitudinales , Masculino , Papillomaviridae , Prevalencia , Conducta Sexual , Parejas SexualesRESUMEN
BACKGROUND: Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution. RESULTS: A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%-48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections. CONCLUSIONS: A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.